EP0727230A2 - Utilization of biocompatible adhesive/sealant materials for securing surgical devices - Google Patents
Utilization of biocompatible adhesive/sealant materials for securing surgical devices Download PDFInfo
- Publication number
- EP0727230A2 EP0727230A2 EP96300790A EP96300790A EP0727230A2 EP 0727230 A2 EP0727230 A2 EP 0727230A2 EP 96300790 A EP96300790 A EP 96300790A EP 96300790 A EP96300790 A EP 96300790A EP 0727230 A2 EP0727230 A2 EP 0727230A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- group
- sealant
- formula
- repeating units
- adhesive
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
Definitions
- This invention relates to securing surgical repair devices to tissue, more specifically this invention relates to securing surgical devices such as screws, plates, bone pins and anchors to bone tissue.
- absorbable suture anchors have been proposed as a replacement for metallic suture anchors.
- the perceived advantage of an absorbable anchor over the metallic anchor is that after the healing process for the cartilage or ligament is complete the anchor will be absorbed by the patient's body and disappear.
- bioabsorbable materials are not strong enough to dig into bone tissue. Therefore, bioabsorbable bone anchors tend to have less resistance to being pulled out of the location in which it is secured.
- an implantable surgical device comprising an implantable surgical device coated with a biocompatible adhesive or sealant.
- the present invention provides a process for using a surgical device that improves the security and placement of the surgical device in a mammalian body. Also described is an implantable surgical device which has been coated with a biocompatible adhesive or sealant in an amount sufficient to facilitate the placement of the surgical device in the desired location in a patient.
- Suitable surgical devices which may benefit from having an adhesive or sealant coating include but are not limited to surgical screws, pins, plates, anchors, rods, clamps, clips, staples, rivets, hooks, buttons, snaps and the like.
- the surgical devices may be made from a biocompatible material using conventional fabrication methods.
- the clips can be composed of various biocompatible metals, e.g. titanium and tantalum, and polymeric materials.
- Preferred bioabsorbable polymeric materials include homopolymers and copolymers of epsilon-caprolactone, glycolide, lactide, para-dioxanone, and trimethylene carbonate.
- Preferred non-absorbable polymers include nylons, polyesters and polypropylene. All these materials have been demonstrated to be biologically acceptable when used as sutures or other implantable medical devices.
- the preferred means for fabricating surgical devices from polymeric materials is to inject a suitable polymer melt into an appropriately designed mold at process conditions conventionally employed for such polymer systems. After the polymer melt cools, the molded polymer shaped in the mold to meet the design criteria of the device can be readily released from the mold.
- Preferred monomers of formula (I) for use in this invention are alpha-cyanoacrylates. These monomers are known in the art and have the formula wherein R 3 is hydrogen and R 4 is a hydrocarbon or substituted hydrocarbon group; a group having the formula -R 5 -O-R 6 -O-R 7 , wherein R 5 is a 1,2-alkylene group having 2-4 carbon atoms, R 6 is an alkylene group having 2-4 carbon atoms, and R 7 is an alkyl group having 1-6 carbon atoms; or a group having the formula: wherein R 8 is or -C(CH 3 ) 2 - and R 9 is an organic radical.
- suitable hydrocarbon and substituted hydrocarbon groups include straight chain or branched chain alkyl groups having 1-16 carbon atoms; straight chain or branched chain C 1 -C 16 alkyl groups substituted with one or more biologically compatible substituents such as an acyloxy group, an alkoxy group, an aryloxy group, a haloalkyl group, a halogen atom, a dialkylamino group, an alkylarylamino group, or a cyano group; straight chain or branched chain alkenyl groups having 2 to 16 carbon atoms; straight chain or branched chain alkynyl groups having 2 to 12 carbon atoms; cycloalkyl groups; arylalkyl groups; alkylaryl groups and aryl groups
- R 4 is preferably an alkyl group having 1-10 carbon atoms or a group having the formula -AOR 10 , wherein A is a divalent straight or branched chain alkylene or oxyalkylene radical having 2-8 carbon atoms, and R 10 is a straight or branched alkyl radical having 1-8 carbon atoms.
- groups represented by the formula -AOR 10 include 1-methoxy-2-propyl, 2-butoxy ethyl, isopropoxy-ethyl, and 2-ethoxy ethyl.
- alpha-cyanoacrylate monomers used in this invention are methyl alpha-cyanoacrylate, butyl alpha-cyanoacrylate, octyl alpha-cyanoacrylate, 1-methoxy-2-propyl cyanoacrylate, 2-butoxy ethyl cyanoacrylate, and isopropoxy-ethyl cyanoacrylate.
- the alpha-cyanoacrylates of formula (II) wherein R 4 is a hydrocarbon or substituted hydrocarbon group can be prepared according to methods known in the art. Reference is made, for example, to U.S. Patents Nos. 2,721,858 and 3,254,111, each of which is hereby incorporated by reference herein.
- the alpha-cyanoacrylates can be prepared by reacting an alkyl cyanoacetate with formaldehyde in a non-aqueous organic solvent and in the presence of a basic catalyst, followed by pyrolysis of the anhydrous intermediate polymer in the presence of a polymerization inhibitor.
- the alpha-cyanoacrylate monomers prepared with low moisture content and essentially free of impurities are preferred for biomedical use.
- alpha-cyanoacrylates of formula (II) wherein R 4 is a group having the formula R 3 -O-R 6 -O-R 7 can be prepared according to the method disclosed in U.S. Patent No. 4,364,876 (Kimura et al.), which is hereby incorporated by reference herein. In the Kimura et al.
- the alpha-cyanoacrylates are prepared by producing a cyanoacetate by esterifying cyanoacetic acid with an alcohol or by transesterifying an alkyl cyanoacetate and an alcohol; condensing the cyanoacetate and formaldehyde or para-formaldehyde.in the presence of a catalyst at a molar ratio of 0.5-1.5:1, preferably 0.8-1.2:1, to obtain a condensate; depolymerizing the condensation reaction mixture either directly or after removal of the condensation catalyst to yield crude cyanoacrylate; and distilling the crude cyanoacrylate to form a high purity cyanoacrylate.
- alpha-cyanoacrylates of formula (II) wherein R 4 is a group having the formula can be prepared according to the procedure described in U.S. Patent No. 3,995,641 (Kronenthal et al.), which is hereby incorporated by reference herein.
- Kronenthal et al. method such alpha-cyanoacrylate monomers are prepared by reacting an alkyl ester of an alpha-cyanoacrylic acid with a cyclic 1,3-diene to form a Diels-Alder adduct which is then subjected to alkaline hydrolysis followed by acidification to form the corresponding alpha-cyanoacrylic acid adduct.
- the alpha-cyanoacrylic acid adduct is preferably esterified by an alkyl bromoacetate to yield the corresponding carbalkoxymethyl alpha-cyanoacrylate adduct.
- the alpha-cyanoacrylic acid adduct may be converted to the alpha-cyanoacrylyl halide adduct by reaction with thionyl chloride.
- the alpha-cyanoacrylyl halide adduct is then reacted with an alkyl hydroxyacetate or a methyl substituted alkyl hydroxyacetate to yield the corresponding carbalkoxymethyl alpha-cyanoacrylate adduct or carbalkoxy alkyl alpha-cyanoacrylate adduct, respectively.
- the cyclic 1,3-diene blocking group is finally removed and the carbalkoxy methyl alpha-cyanoacrylate adduct or the carbalkoxy alkyl alpha-cyanoacrylate adduct is converted into the corresponding carbalkoxy alkyl alpha-cyanoacrylate by heating the adduct in the presence of a slight deficit of maleic anhydride.
- the monomers of formula (IV) wherein R 4 is an alkyl group of 1-10 carbon atoms can be prepared by reacting an appropriate 2-cyanoacetate with acrolein in the presence of a catalyst such as zinc chloride.
- a catalyst such as zinc chloride.
- a biocompatibilizing agent may be added to the cyanoacrylate adhesive such as are disclosed in U.S. Patent 5,328,687, hereby incorporated by reference.
- Suitable bioabsorbable sealants include semi-crystalline aliphatic ester homopolymers, and copolymers made from polymers of the formula: (VI) [-O-R 11 -C(O)-] Y , wherein R 11 is selected from the group consisting of-CR 12 H-, -(CH 2 ) 3 -O-, -CH 2 -CH 2 -O-CH 2 -, CR 12 H-CH 2 , -(CH 2 ) 4 -,-(CH 2 ) z -O-C(O)- and -(CH 2 ) z -C(O)-CH 2 -; R 12 is hydrogen or methyl; z is an integer in the range of from 1 to 7; and y is an integer in the range of from about 10 to about 20,000.
- bioabsorbable aliphatic ester polymers that are semi-crystalline solids at room temperature, may be used in the present invention.
- the polymers of this invention are generally characterized as being solids at body temperature (37°C) and preferably will be melt at temperatures of less than 60°C.
- Suitable bioabsorbable polymers include solid poly( ⁇ -caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) homopolymers and copolymers of ⁇ -caprolactone and trimethylene carbonate.
- Copolymers of ⁇ -caprolactone should be composed of from about 100 mole percent to about 70 mole percent and preferably from 95 mole percent to 85 mole percent of ⁇ -caprolactone repeating units with the remainder of the polymer being a plurality of second lactone repeating units.
- the second lactone repeating units will be selected from the group consisting of glycolide repeating units, lactide repeating units, 1,4-dioxanone repeating units, 1,4-dioxepan-2-one repeating units, 1,5-dioxepan-2-one repeating units, trimethylene carbonate repeating units, and combinations thereof.
- the solid polymers of trimethylene carbonate should be composed of from in the range of from about 1 to about 20 mole percent or from about 100 to about 80 mole percent of trimethylene carbonate with the remainder of the copolymer being composed of a plurality of lactone repeating units selected from the group consisting of glycolide repeating units, lactide repeating units, p-dioxanone repeating units, ⁇ -caprolactone repeating units, and combinations thereof.
- trimethylene carbonate copolymers it is preferred for the trimethylene carbonate copolymers to have crystalline regions formed by the second lactone repeating units wherein the crystalline regions provide at least 5 percent crystallinity to the final copolymer.
- the solid polymers may be linear, branched, or star branched; block copolymers or terpolymers; segmented block copolymers or terpolymers. These polymers will also be purified to substantially remove unreacted monomers which may cause an inflammatory reaction in tissue.
- the most preferred polymers for use as the adhesive/sealant are semicrystalline polymers selected from the group consisting of poly( ⁇ -caprolactone), poly( ⁇ -caprolactone-co-trimethylene carbonate), poly( ⁇ -caprolactone-co-lactide), poly( ⁇ -caprolactone-co-p-dioxanone), and poly( ⁇ -caprolactone-co-glycolide).
- the mole percent of ⁇ -caprolactone repeating units in these polymers should be in the range of from 100 to about 80 mole percent and preferably in the range of from 95 to 85 mole percent. Most preferably these polymers will be statistically random copolymers.
- the polymers used as the adhesive/sealant should have an inherent viscosity as determined in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) at 25°C ranging from about 0.1 dL/g to about 2.0 dL/g, preferably from about 0.15 dL/g to about 1.5 dL/g, and most preferably from 0.2 dL/g to 1.0 dL/g.
- a polymer with an inherent viscosity below 0.1 dL/g may fail to crystallize at room temperature, and a polymer with an inherent viscosity above 2.0 dL/g may make the polymer have too high of a melting point.
- the aliphatic poly(ester)s are generally prepared by a ring opening polymerization of the desired proportions of one or more lactone monomers in the presence of an organometallic catalyst and an initiator at elevated temperatures.
- the organometallic catalyst is preferably a tin-based catalyst, e.g. stannous octoate, and is present in the monomer mixture at a molar ratio of monomer to catalyst ranging from about 15,000/1 to about 80,000/1.
- the initiator is typically an alkanol (such as 1-dodecanol), a polyol (such as 1,2-propanediol, 1,3-propanediol, diethylene glycol, or glycerol, poly(ethylene glycol)s, poly(propylene glycol)s and poly(ethylene-co-propylene glycol)s), a hydroxyacid, or an amine, and is present in the monomer mixture at a molar ratio of monomer to initiator ranging from about 100/1 to about 5000/1.
- the polymerization is typically carried out at a temperature range from about 80 to about 220°C, preferably 160 to 190°C, until the desired molecular weight and viscosity are achieved.
- Suitable bioabsorbable sealants include calcium containing compounds with the general formula: M 2+ 10-n N 1+ 2n (WO 4 3- ) 6 mU X- where n is an integer from 1 to 10, and m is 2 when x is 1, or m is 1 when x is 2, M and N are alkali or alkaline earth metals, preferably calcium, magnesium, sodium, zinc, and potassium.
- WO 4 is an acid radical, where W is preferably phosphorus, vanadium, sulfur or silicon, or is substituted in whole or part with carbonate (CO 3 2- ).
- U is an anion, preferably halide, hydroxide, or carbonate.
- calcium containing sealants selected from the group consisting of mono-, di-, octa-, ⁇ -tri-, ⁇ -tri-, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride and mixtures thereof.
- the calcium containing sealants can also contain a bioactive glass comprising metal oxides such as calcium oxide, silicon dioxide, sodium oxide, phosphorus pentoxide, and mixtures thereof, and the like.
- the calcium containing sealants will preferably have a particle size of about 10 microns to about 1000 microns, and more preferably about 100 microns to about 500 microns.
- the calcium containing sealants will generally be applied in an aqueous slurry.
- the amount of calcium containing material in the slurry will generally be in the range from about 10 weight percent to about 90 weight percent.
- the slurry will preferably be retained in place at the desired location until it solidifies or develops a putty like consistency
- the adhesive and/or sealant may be applied to at least one surface of the medical device that is to be contacted with the bone tissue or applied to the site where the surgical device is to be secured.
- the adhesive may be applied to the site where the surgical device is to be secured and the surgical device applied thereafter in an appropriate time so that the adhesive or sealant can set.
- the sealant may serve as a filling and support agent for the medical device. For example, when using a bone plate with multiple openings for fasteners (such as screws), the sealant would be applied to the surface to contact the bone to provide a putty like base on which to mount the bone plate on to simplify installation of the bone plate.
- the adhesives and/or sealants of the present invention will generally be applied in a liquid form.
- the adhesive and/or sealant will generally be applied through a small diameter delivery device such as a syringe, with or without mechanical assistance, a caulking gun, a soft-sided tube, and the like.
- a mechanical stirrer, a stainless steel thermocouple connected to a thermowatch which controlled the immersion heater, and a water cooled distillation apparatus were then installed.
- the still was connected to a dry nitrogen gas line via a Firestone valve.
- the contents of the reaction flask were heated to 100°C for 18 hours; then, the pot temperature was raise until the azeotropic mixture of acetic acid, water, and xylene started to distill out.
- the oil bath temperature ranged from 125°C to 145°C during the distillation.
- the still head temperature varied from 95°C to 110°C. When most of the solvents were removed, the resulting suspension was allowed to cool down to room temperature.
- the material was recrystallized again to produce about 188 grams of doubly recrystallized adduct [82 % recovery; 58 % yield overall; still contained some anthracene].
- the material was recrystallized again yielding 158 grams of triply recrystallized material [84 % recovery; 49 % overall yield].
- the crystals were isolated by suction filtration, washed with methanol, and vacuumed dried at 50°C after each recrystallization.
- DMMM Dimethyl Methylidene Malonate
- the stirrer blade was removed, and the polymer melt was allowed to cool down to room temperature in an inert atmosphere. After about two hours, the polymer started to crystallize and became opaque.
- the polymer was isolated by wrapping the flask in aluminum foil, freezing the flask in liquid nitrogen, and removing the broken glass. Then, the frozen polymer was ground on a Wiley mill and sieved through a screen. 35.2 grams of a fine powder were saved; 161.8 grams of the coarse grounds were vacuum dried at 40°C for 12 hours. 160.9 grams of devolatized PCL were collected. The PCL was vacuum dried again under the same conditions without any weight loss.
- the number average molecular weight was 9,000 g/mol and the weight average molecular weight was 16,000 g/mol as determined by gel permeation chromatography in HFIP using PMMA standards.
- the monomer conversion was 97.6 mole percent as determined by 300 MHz 1 H NMR spectrum in HFAD/C 6 D 6 ; 2.4 mole percent unreacted monomer was also detected.
- the polymer melted between 60°C and 65°C using a Fisher-Johns apparatus.
- Bone Pin Pullout Force Measurements Materials and Methods: Rabbit femurs were cleaned and frozen. They were defrosted before testing and allowed to warm up to 37°C. A hole was drilled in the femoral condyle with a 2.7 mm drill bit. Bone pins made of poly[glycolic acid] having a nominal diameter of 2.8 mm were roughened with sand paper to improve adhesion and were inserted into the femoral condyle with no adhesive, with Vetbond ( n -butyl cyanoacrylate), dimethyl methylene malonate (DMMM) from Example 2 and with low molecular weight poly[ ⁇ -caprolactone] (PCL) from Example 3.
- Vetbond n -butyl cyanoacrylate
- DMMM dimethyl methylene malonate
- PCL low molecular weight poly[ ⁇ -caprolactone]
- the cure time was one minute for the Vetbond and DMMM and thirty minutes for the low molecular weight PCL.
- Mechanical testing was conducted on an Instron model 1122 tensile tester at a cross head speed of 0.5 inches per minute. The femur was held in the bottom fixture, and the bone pin was pulled out by the upper fixture. The force was measured and the maximum force recorded.
Abstract
- (a) a material made from monomers of the formula:
CHR1=CX1Y1
wherein X1 and Y1 are each strong electron withdrawing groups, and R1 is hydrogen or, provided that X1 and Y1 are both cyano groups, a C1-C4 alkyl group; - (b) a semi-crystalline aliphatic poly(ester) of the formula:
[-O-R11-C(O)-]Y,
wherein R11 is selected from the group consisting of -CR12H-, -(CH2)3-O-, -CH2-CH2-O-CH2-, CR12H-CH2, - (CH2)4-, -(CH2)z-O-C(O)- and -(CH2)z-C(O)-CH2-; R12 is hydrogen or methyl; z is an integer in the range of from 1 to 7 and y is an integer in the range of from about 10 to about 20,000; and - (c) a slurry of water and a calcium containing compounds with the general formula:
M2+ 10-nN1+ 2n(WO4 3-)6mU2-
where n is an integer from 1 to 10, and m is 2 when x is 1, or m is 1 when x is 2, M and N are alkali or alkaline earth metals; WO4 is an acid radical and W is phosphorus, vanadium, sulfur, silicon, or is substituted in whole or part with carbonate (CO3 2-);
and U is a halide, hydroxide, or carbonate; provided in an amount effective to increase the amount of force necessary to remove the implanted surgical device. Additionally provided is a surgical device that is at least partially coated with at least one biocompatible adhesive and/or sealant.
Description
- This invention relates to securing surgical repair devices to tissue, more specifically this invention relates to securing surgical devices such as screws, plates, bone pins and anchors to bone tissue.
- In orthopedic surgery it is often necessary to reattach cartilage and ligaments to skeletal bones with surgical pins, screws or anchors. For example, metallic suture anchors are currently used to facilitate cartilage or ligament reattachment. In these procedures a hole is drilled into the skeletal bone. A suture anchor, attached to a suture, is then inserted into the hole in a manner that allows the anchor to engage the sides of the hole and be held in place. The suture is then used to secure the torn cartilage or ligament to the bone. However, sometimes during or after the healing process these anchors fail to remain in place and must be removed to avoid harm to the patient.
- Recently, absorbable suture anchors have been proposed as a replacement for metallic suture anchors. The perceived advantage of an absorbable anchor over the metallic anchor is that after the healing process for the cartilage or ligament is complete the anchor will be absorbed by the patient's body and disappear. However, most bioabsorbable materials are not strong enough to dig into bone tissue. Therefore, bioabsorbable bone anchors tend to have less resistance to being pulled out of the location in which it is secured.
- Thus, it would be a significant contribution to the art to provide a method to enhance the secure placement of implantable surgical devices in patients. Additionally, it would be advantageous if a method could be developed to enhance the resistance to removal of bioabsorbable surgical implantable devices.
- We have discovered a process for enhancing the security of implantable surgical devices secured to bone tissue comprising implanting a surgical device with a biocompatible adhesive and/or sealant provided in an amount effective to increase the security of the implanted surgical device.
- In another embodiment of the present invention we have also provided an implantable surgical device comprising an implantable surgical device coated with a biocompatible adhesive or sealant.
- The present invention provides a process for using a surgical device that improves the security and placement of the surgical device in a mammalian body. Also described is an implantable surgical device which has been coated with a biocompatible adhesive or sealant in an amount sufficient to facilitate the placement of the surgical device in the desired location in a patient. Suitable surgical devices which may benefit from having an adhesive or sealant coating include but are not limited to surgical screws, pins, plates, anchors, rods, clamps, clips, staples, rivets, hooks, buttons, snaps and the like.
- These surgical devices may be made from a biocompatible material using conventional fabrication methods. The clips can be composed of various biocompatible metals, e.g. titanium and tantalum, and polymeric materials. Preferred bioabsorbable polymeric materials include homopolymers and copolymers of epsilon-caprolactone, glycolide, lactide, para-dioxanone, and trimethylene carbonate. Preferred non-absorbable polymers include nylons, polyesters and polypropylene. All these materials have been demonstrated to be biologically acceptable when used as sutures or other implantable medical devices.
- The preferred means for fabricating surgical devices from polymeric materials is to inject a suitable polymer melt into an appropriately designed mold at process conditions conventionally employed for such polymer systems. After the polymer melt cools, the molded polymer shaped in the mold to meet the design criteria of the device can be readily released from the mold.
- One class of suitable biocompatible adhesives or sealants that can be used in the practice of the present invention include materials made from monomers of the formula:
(I) CHR1=CX1Y1
wherein X1 and Y1 are each strong electron withdrawing groups, and R1 is hydrogen or, provided that X1 and Y1 are both cyano groups, a C1-C4 alkyl group. Examples of monomers within the scope of formula (I) include α-cyanoacrylates, vinylidene cyanides, C1-C4 alkyl homologues of vinylidene cyanides, dialkyl methylene malonates, acylacrylonitriles, vinyl sulfinates, and vinyl sulfonates of the formula CH2=CX2Y2 wherein X2 is SO2R2 or -SO3R2 and Y2 is -CN, COOR2, COCH3, -SO2R2 or -SO3R2 and R2 is hydrogen or an alkyl group. - Preferred monomers of formula (I) for use in this invention are alpha-cyanoacrylates. These monomers are known in the art and have the formula
- Examples of suitable hydrocarbon and substituted hydrocarbon groups include straight chain or branched chain alkyl groups having 1-16 carbon atoms; straight chain or branched chain C1-C16 alkyl groups substituted with one or more biologically compatible substituents such as an acyloxy group, an alkoxy group, an aryloxy group, a haloalkyl group, a halogen atom, a dialkylamino group, an alkylarylamino group, or a cyano group; straight chain or branched chain alkenyl groups having 2 to 16 carbon atoms; straight chain or branched chain alkynyl groups having 2 to 12 carbon atoms; cycloalkyl groups; arylalkyl groups; alkylaryl groups and aryl groups
- In the cyanoacrylate monomer of formula (II), R4 is preferably an alkyl group having 1-10 carbon atoms or a group having the formula -AOR10, wherein A is a divalent straight or branched chain alkylene or oxyalkylene radical having 2-8 carbon atoms, and R10 is a straight or branched alkyl radical having 1-8 carbon atoms. Examples of groups represented by the formula -AOR10 include 1-methoxy-2-propyl, 2-butoxy ethyl, isopropoxy-ethyl, and 2-ethoxy ethyl.
- The most preferred alpha-cyanoacrylate monomers used in this invention are methyl alpha-cyanoacrylate, butyl alpha-cyanoacrylate, octyl alpha-cyanoacrylate, 1-methoxy-2-propyl cyanoacrylate, 2-butoxy ethyl cyanoacrylate, and isopropoxy-ethyl cyanoacrylate.
- The alpha-cyanoacrylates of formula (II) wherein R4 is a hydrocarbon or substituted hydrocarbon group can be prepared according to methods known in the art. Reference is made, for example, to U.S. Patents Nos. 2,721,858 and 3,254,111, each of which is hereby incorporated by reference herein. For example, the alpha-cyanoacrylates can be prepared by reacting an alkyl cyanoacetate with formaldehyde in a non-aqueous organic solvent and in the presence of a basic catalyst, followed by pyrolysis of the anhydrous intermediate polymer in the presence of a polymerization inhibitor. The alpha-cyanoacrylate monomers prepared with low moisture content and essentially free of impurities are preferred for biomedical use.
- The alpha-cyanoacrylates of formula (II) wherein R4 is a group having the formula R3-O-R6-O-R7 can be prepared according to the method disclosed in U.S. Patent No. 4,364,876 (Kimura et al.), which is hereby incorporated by reference herein. In the Kimura et al. method, the alpha-cyanoacrylates are prepared by producing a cyanoacetate by esterifying cyanoacetic acid with an alcohol or by transesterifying an alkyl cyanoacetate and an alcohol; condensing the cyanoacetate and formaldehyde or para-formaldehyde.in the presence of a catalyst at a molar ratio of 0.5-1.5:1, preferably 0.8-1.2:1, to obtain a condensate; depolymerizing the condensation reaction mixture either directly or after removal of the condensation catalyst to yield crude cyanoacrylate; and distilling the crude cyanoacrylate to form a high purity cyanoacrylate.
- The alpha-cyanoacrylates of formula (II) wherein R4 is a group having the formula
- Alternatively, the alpha-cyanoacrylic acid adduct may be converted to the alpha-cyanoacrylyl halide adduct by reaction with thionyl chloride. The alpha-cyanoacrylyl halide adduct is then reacted with an alkyl hydroxyacetate or a methyl substituted alkyl hydroxyacetate to yield the corresponding carbalkoxymethyl alpha-cyanoacrylate adduct or carbalkoxy alkyl alpha-cyanoacrylate adduct, respectively. The cyclic 1,3-diene blocking group is finally removed and the carbalkoxy methyl alpha-cyanoacrylate adduct or the carbalkoxy alkyl alpha-cyanoacrylate adduct is converted into the corresponding carbalkoxy alkyl alpha-cyanoacrylate by heating the adduct in the presence of a slight deficit of maleic anhydride.
- Another type of biocompatible adhesives or sealant that may be used in the practice of the present invention are copolymers of formula (I) or one monomer of formula (I) and a monomer of the formula:
(IV) CHZ=CX1Y1
wherein X1 and Y1 are as described for formula (I) and Z is -CH=CH2. Examples of monomers of formula (IV) include cyanopentadienoates and alpha-cyanoacrylates of the formula: - Optionally, a biocompatibilizing agent may be added to the cyanoacrylate adhesive such as are disclosed in U.S. Patent 5,328,687, hereby incorporated by reference.
- Suitable bioabsorbable sealants include semi-crystalline aliphatic ester homopolymers, and copolymers made from polymers of the formula:
(VI) [-O-R11-C(O)-]Y,
wherein R11 is selected from the group consisting of-CR12H-, -(CH2)3-O-, -CH2-CH2-O-CH2-, CR12H-CH2, -(CH2)4-,-(CH2)z-O-C(O)- and -(CH2)z-C(O)-CH2-; R12 is hydrogen or methyl; z is an integer in the range of from 1 to 7; and y is an integer in the range of from about 10 to about 20,000. - Many nontoxic bioabsorbable aliphatic ester polymers that are semi-crystalline solids at room temperature, may be used in the present invention. The polymers of this invention are generally characterized as being solids at body temperature (37°C) and preferably will be melt at temperatures of less than 60°C. Suitable bioabsorbable polymers include solid poly(ε-caprolactone), poly(p-dioxanone), or poly(trimethylene carbonate) homopolymers and copolymers of ε-caprolactone and trimethylene carbonate. Copolymers of ε-caprolactone should be composed of from about 100 mole percent to about 70 mole percent and preferably from 95 mole percent to 85 mole percent of ε-caprolactone repeating units with the remainder of the polymer being a plurality of second lactone repeating units. The second lactone repeating units will be selected from the group consisting of glycolide repeating units, lactide repeating units, 1,4-dioxanone repeating units, 1,4-dioxepan-2-one repeating units, 1,5-dioxepan-2-one repeating units, trimethylene carbonate repeating units, and combinations thereof. Preferred are copolymers of ε-caprolactone that are semicrystalline solids at body temperature. The solid polymers of trimethylene carbonate should be composed of from in the range of from about 1 to about 20 mole percent or from about 100 to about 80 mole percent of trimethylene carbonate with the remainder of the copolymer being composed of a plurality of lactone repeating units selected from the group consisting of glycolide repeating units, lactide repeating units, p-dioxanone repeating units, ε-caprolactone repeating units, and combinations thereof.
- It is preferred for the trimethylene carbonate copolymers to have crystalline regions formed by the second lactone repeating units wherein the crystalline regions provide at least 5 percent crystallinity to the final copolymer. The solid polymers may be linear, branched, or star branched; block copolymers or terpolymers; segmented block copolymers or terpolymers. These polymers will also be purified to substantially remove unreacted monomers which may cause an inflammatory reaction in tissue.
- The most preferred polymers for use as the adhesive/sealant are semicrystalline polymers selected from the group consisting of poly(ε-caprolactone), poly(ε-caprolactone-co-trimethylene carbonate), poly(ε-caprolactone-co-lactide), poly(ε-caprolactone-co-p-dioxanone), and poly(ε-caprolactone-co-glycolide). The mole percent of ε-caprolactone repeating units in these polymers should be in the range of from 100 to about 80 mole percent and preferably in the range of from 95 to 85 mole percent. Most preferably these polymers will be statistically random copolymers.
- The polymers used as the adhesive/sealant should have an inherent viscosity as determined in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) at 25°C ranging from about 0.1 dL/g to about 2.0 dL/g, preferably from about 0.15 dL/g to about 1.5 dL/g, and most preferably from 0.2 dL/g to 1.0 dL/g. A polymer with an inherent viscosity below 0.1 dL/g may fail to crystallize at room temperature, and a polymer with an inherent viscosity above 2.0 dL/g may make the polymer have too high of a melting point.
- The aliphatic poly(ester)s are generally prepared by a ring opening polymerization of the desired proportions of one or more lactone monomers in the presence of an organometallic catalyst and an initiator at elevated temperatures. The organometallic catalyst is preferably a tin-based catalyst, e.g. stannous octoate, and is present in the monomer mixture at a molar ratio of monomer to catalyst ranging from about 15,000/1 to about 80,000/1. The initiator is typically an alkanol (such as 1-dodecanol), a polyol (such as 1,2-propanediol, 1,3-propanediol, diethylene glycol, or glycerol, poly(ethylene glycol)s, poly(propylene glycol)s and poly(ethylene-co-propylene glycol)s), a hydroxyacid, or an amine, and is present in the monomer mixture at a molar ratio of monomer to initiator ranging from about 100/1 to about 5000/1. The polymerization is typically carried out at a temperature range from about 80 to about 220°C, preferably 160 to 190°C, until the desired molecular weight and viscosity are achieved.
- The aliphatic polyesters described above will be solids at room temperature but may be heated to provide a putty like or liquid material that may be applied as a sealant to support surgical devices or to secure a surgical device. In one embodiment of the present invention, the aliphatic polyester would be heated to its melting point and applied to the desired location before it resolidifed. In this embodiment, if a bone pin were inserted in a hole drilled in bone tissue, melted polyester would be poured into the hole before or after the pin was insert to help secure the bone pin in the bone tissue. Alternatively, the aliphatic polyester could be heated until it softens and then used as a putty and placed at the desired location and act as a filler.
- Other suitable bioabsorbable sealants include calcium containing compounds with the general formula:
M2+ 10-nN1+ 2n(WO4 3-)6mUX-
where n is an integer from 1 to 10, and m is 2 when x is 1, or m is 1 when x is 2, M and N are alkali or alkaline earth metals, preferably calcium, magnesium, sodium, zinc, and potassium. WO4 is an acid radical, where W is preferably phosphorus, vanadium, sulfur or silicon, or is substituted in whole or part with carbonate (CO3 2-). U is an anion, preferably halide, hydroxide, or carbonate. - Most preferred are calcium containing sealants selected from the group consisting of mono-, di-, octa-, α-tri-, β-tri-, or tetra-calcium phosphate, hydroxyapatite, fluorapatite, calcium sulfate, calcium fluoride and mixtures thereof.
- The calcium containing sealants can also contain a bioactive glass comprising metal oxides such as calcium oxide, silicon dioxide, sodium oxide, phosphorus pentoxide, and mixtures thereof, and the like. The calcium containing sealants will preferably have a particle size of about 10 microns to about 1000 microns, and more preferably about 100 microns to about 500 microns.
- The calcium containing sealants will generally be applied in an aqueous slurry. The amount of calcium containing material in the slurry will generally be in the range from about 10 weight percent to about 90 weight percent. The slurry will preferably be retained in place at the desired location until it solidifies or develops a putty like consistency
- The adhesive and/or sealant may be applied to at least one surface of the medical device that is to be contacted with the bone tissue or applied to the site where the surgical device is to be secured. For example, when a bone pin or anchor is placed in a hole drilled in bone tissue the pin or anchor surfaces that will contact the bone tissue will be coated with adhesive and placed in intimate contact with the bone tissue. The adhesive will then adhere to the device and the bone and enhance the security of the pin or anchor in the hole. Alternatively, the adhesive may be applied to the site where the surgical device is to be secured and the surgical device applied thereafter in an appropriate time so that the adhesive or sealant can set. If a sealant is used the sealant may serve as a filling and support agent for the medical device. For example, when using a bone plate with multiple openings for fasteners (such as screws), the sealant would be applied to the surface to contact the bone to provide a putty like base on which to mount the bone plate on to simplify installation of the bone plate.
- Those skilled in the art will readily be able to determine the appropriate amount of adhesive and/or sealant to apply in a given surgical application. Similarly, the amount of an adhesive and/or sealant to be applied to a surgical device before implantation will be a discretionary matter depending on the operation and the specific circumstances of the operation.
- The adhesives and/or sealants of the present invention will generally be applied in a liquid form. The adhesive and/or sealant will generally be applied through a small diameter delivery device such as a syringe, with or without mechanical assistance, a caulking gun, a soft-sided tube, and the like.
- The following nonlimiting examples are provided to illustrate the practice of the present invention.
- Synthesis of the Anthracene Adduct of Dimethyl Methylidene Malonate. 178.0 grams (1.00 mol) of powdered anthracene, 60.0 grams (2.00 mol) of powdered paraformaldehyde, 132.0 grams (1.00 mol) of dimethyl malonate, 10.0 grams (50 mmol) of cupric acetate monohydrate, 225 mL of glacial acetic acid, and 450 mL of xylene were added to a two liter, three necked, round bottom flask. In the exhaust hood, the flask was immersed into an oil bath and secured with a clamp. A mechanical stirrer, a stainless steel thermocouple connected to a thermowatch which controlled the immersion heater, and a water cooled distillation apparatus were then installed. The still was connected to a dry nitrogen gas line via a Firestone valve. The contents of the reaction flask were heated to 100°C for 18 hours; then, the pot temperature was raise until the azeotropic mixture of acetic acid, water, and xylene started to distill out. The oil bath temperature ranged from 125°C to 145°C during the distillation. The still head temperature varied from 95°C to 110°C. When most of the solvents were removed, the resulting suspension was allowed to cool down to room temperature. The residue was dissolved in chloroform, and in portions, transferred into a separatory funnel, washed with an equal volume of saturated ammonium chloride solution, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and suction filtered. The filtrate was transferred into a round bottom flask and the chloroform removed by evaporation. The crude product [305 grams; 95 % yield, but impure] was then recrystallized from xylene [1 gram/2 mL] using activated charcoal at -5°C. 228 grams of recrystallized adduct were collected [75 % recovery; 71 % yield overall, although the material is still contaminated with small amounts of anthracene]. The material was recrystallized again to produce about 188 grams of doubly recrystallized adduct [82 % recovery; 58 % yield overall; still contained some anthracene]. The material was recrystallized again yielding 158 grams of triply recrystallized material [84 % recovery; 49 % overall yield]. The crystals were isolated by suction filtration, washed with methanol, and vacuumed dried at 50°C after each recrystallization.
- Synthesis of Dimethyl Methylidene Malonate (DMMM). 500 grams of mineral oil, 120.0 grams (373 mmol) of the anthracene adduct of dimethyl methylidene malonate, 64.9 grams (375 mmol) of N-phenylmaleimide, and 0.50 grams (3.5 mmol) of phosphorous pentoxide were added to a silanized, flame dried, one liter round bottom flask containing a magnetic stirring bar. This mixture was degassed on a vacuum manifold overnight. Then, a silanized distillation head and fraction cutter were installed, and the flask immersed in an oil bath already set at 225°C under a nitrogen atmosphere. After fifteen minutes, a yellow solution was obtained. One hour later, the oil bath was removed and the contents of the flask were allowed to cool down to 50°C. High vacuum was then applied to the reaction system. A pressure of around 450 microns was typical in the beginning of the distillation, and the pressure fell to around 300 microns by the end of the distillation. Once the system stabilized at low pressure, the dimethyl methylidene malonate distilled over between 50°C and 55°C [the oil bath temperature ranged from 50°C to around 70°C]. 31.0 grams of dimethyl methylidene malonate were collected in the middle fraction [58 % yield; > 99 mole % pure by NMR spectroscopy].
- Synthesis of Poly[ε-caprolactone] (PCL). In the glove box, 120 µL (40 µmol) of a 0.33 M stannous octoate solution in toluene, 2.3 mL (24 mmol) of distilled diethylene glycol, and 205.3 grams (1.8 mol) of distilled ε-caprolactone were transferred into a silanized, flame dried, 500 mL, round bottom flask equipped with a stainless steel mechanical stirrer and a nitrogen gas blanket. The reaction flask was immersed in an oil bath already set at 75°C. After fifteen minutes, a clear solution was obtained and then the oil bath temperature was raised to 190°C for 19 hours. The stirrer blade was removed, and the polymer melt was allowed to cool down to room temperature in an inert atmosphere. After about two hours, the polymer started to crystallize and became opaque. The polymer was isolated by wrapping the flask in aluminum foil, freezing the flask in liquid nitrogen, and removing the broken glass. Then, the frozen polymer was ground on a Wiley mill and sieved through a screen. 35.2 grams of a fine powder were saved; 161.8 grams of the coarse grounds were vacuum dried at 40°C for 12 hours. 160.9 grams of devolatized PCL were collected. The PCL was vacuum dried again under the same conditions without any weight loss. The inherent viscosity was measured in chloroform at 25°C and found to be 0.3 dL/g [c = 0.10 g/dL]. The number average molecular weight was 9,000 g/mol and the weight average molecular weight was 16,000 g/mol as determined by gel permeation chromatography in HFIP using PMMA standards. The monomer conversion was 97.6 mole percent as determined by 300 MHz 1H NMR spectrum in HFAD/C6D6; 2.4 mole percent unreacted monomer was also detected. The polymer melted between 60°C and 65°C using a Fisher-Johns apparatus.
- In the glove box, 25 grams of PCL and 0.25 grams of sucrose [a nucleating agent] were added to a silanized, flame dried, 100 mL, round bottom flask equipped with a stainless steel mechanical stirrer and a nitrogen gas blanket. The reaction flask was immersed in an oil bath set at 125°C. After the PCL had melted, the mixture was blended for one hour and then allowed to cool down to room temperature under an inert atmosphere. The polymer was isolated by wrapping the flask in aluminum foil, freezing the flask in liquid nitrogen, and removing the broken glass. The frozen polymer was crushed and vacuum dried at room temperature overnight and then stored under nitrogen gas until used in the bone pin study described below.
- Bone Pin Pullout Force Measurements. Materials and Methods: Rabbit femurs were cleaned and frozen. They were defrosted before testing and allowed to warm up to 37°C. A hole was drilled in the femoral condyle with a 2.7 mm drill bit. Bone pins made of poly[glycolic acid] having a nominal diameter of 2.8 mm were roughened with sand paper to improve adhesion and were inserted into the femoral condyle with no adhesive, with Vetbond (n-butyl cyanoacrylate), dimethyl methylene malonate (DMMM) from Example 2 and with low molecular weight poly[ε-caprolactone] (PCL) from Example 3. The cure time was one minute for the Vetbond and DMMM and thirty minutes for the low molecular weight PCL. Mechanical testing was conducted on an Instron model 1122 tensile tester at a cross head speed of 0.5 inches per minute. The femur was held in the bottom fixture, and the bone pin was pulled out by the upper fixture. The force was measured and the maximum force recorded.
- Results: The pullout force data are summarized in Table 1. These data clearly show that the average pullout force increased significantly when an adhesive was used; the increase in pullout strength varied from 4 to 11 times that of the force needed to remove the bone pin without any glue being applied.
Table 1. Pullout Strengths Pullout Strengths (kg) Test Bone Pin Only Vetbond DMMM PCL 1 0.661 6.95 3.43 2.3 2 0.765 8.35 7.41 2.94 3 -- 9.82 6.79 2.19 4 -- 5.66 2.27 3.41 Average 0.71 7.70 4.98 2.71
Claims (9)
- A biocompatible adhesive and/or sealant for enhancing the security of implantable surgical devices secured to bone tissue, selected from the group consisting of:(a) a material made from monomers of the formula:
CHR1=CX1Y1
wherein X1 and Y1 are each strong electron withdrawing groups, and R1 is hydrogen or, provided that X1 and Y1 are both cyano groups, a C1-C4 alkyl group;(b) a bioabsorbable semi-crystalline aliphatic poly(ester) of the formula:
[-O-R11-C(O)-]y,
wherein R11 is selected from the group consisting of -CR12H-, -(CH2)3-O-,-CH2-CH2-O-CH2-,-CR12H-CH2-, -(CH2)4-, -(CH2)z-O-C(O)- and -(CH2)z-C(O)-CH2-; R12 is hydrogen or methyl; z is an integer in the range of from 1 to 7; and y is an integer in the range of from 10 to 20,000; and(c) a slurry of water and a calcium containing compound with the general formula:
10-n(M2+).2n(N1+).6(WO4 3-).m(Ux-)
wherein n is an integer from 1 to 10, and m is 2 when x is 1, or m is 1 when x is 2, M and N are alkali or alkaline earth metals; WO4 is an acid radical and W is phosphorus, vanadium, sulfur, silicon, or is substituted in whole or part with carbonate (CO3 2-); and U is a halide, hydroxide or carbonate. - The adhesive and/or sealant of claim 1 which is selected from the group consisting of α-cyanoacrylates, vinylidene cyanides, C1-C4 alkyl homologues of vinylidene cyanides, dialkyl methylene malonates, acylacrylonitriles, vinyl sulfinates and vinyl sulfonates.
- The adhesive and/or sealant of claim 2 which is selected from the group consisting of materials having the formula:
-R5-O-R6-R7
wherein R5 is a 1,2-alkylene group having 2 to 4 carbon atoms, R6 is an alkylene group having 2 to 4 carbon atoms, and R7 is an alkyl group having 1 to 6 carbon atoms; or a group having the formula
- R8 - C(O) - 0 - R9
wherein R8 is -CH2-, -CH(CH3)-, or -C(CH3)2 and R9 is an organic radical. - The adhesive and/or sealant of claim 1 or claim 2 which is selected from the group consisting of methyl alpha-cyanoacrylate, butyl alpha-cyanoacrylate, octyl alpha-cyanoacrylate, 1-methoxy-2-propyl cyanoacrylate, 2-butoxy ethyl cyanoacrylate, and isopropoxy-ethyl cyanoacrylate.
- The adhesive and/or sealant of claim 1 which is a bioabsorbable semi-crystalline aliphatic poly(ester) homopolymer selected from the group consisting of poly(ε-caprolactone), poly(p-dioxanone), and poly(trimethylene carbonate).
- The adhesive and/or sealant or claim 1 which is a bioabsorbable semi-crystalline aliphatic poly(ester) copolymer composed of from 100 mole percent to 70 mole percent of ε-caprolactone repeating units with the remainder of the polymer being a plurality of second lactone repeating units selected from the group consisting of glycolide repeating units, lactide repeating units, 1,4-dioxanone repeating units, 1,4-dioxepan-2-one repeating units, 1,5-dioxepan-2-one repeating units, trimethylene carbonate repeating units, and combinations thereof.
- An implantable surgical device that is at least partially coated with a biocompatible adhesive and/or sealant according to any one of claims 1 to 6 in an amount effective to increase the amount of force necessary to remove the implanted surgical device.
- The surgical devices of claim 7 which is selected from the group consisting of screws, pins, plates, anchors, rods, clamps, clips, staples, rivets, hooks, buttons and snaps.
- The surgical device of claim 7 or claim 8 which is made of a bioabsorbable polymeric material.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/385,015 US5550172A (en) | 1995-02-07 | 1995-02-07 | Utilization of biocompatible adhesive/sealant materials for securing surgical devices |
US385015 | 1995-02-07 |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0727230A2 true EP0727230A2 (en) | 1996-08-21 |
EP0727230A3 EP0727230A3 (en) | 1999-02-03 |
EP0727230B1 EP0727230B1 (en) | 2007-05-16 |
Family
ID=23519689
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP96300790A Expired - Lifetime EP0727230B1 (en) | 1995-02-07 | 1996-02-06 | Utilization of biocompatible adhesive/sealant materials for securing surgical devices |
Country Status (8)
Country | Link |
---|---|
US (1) | US5550172A (en) |
EP (1) | EP0727230B1 (en) |
JP (1) | JPH08252306A (en) |
AU (1) | AU4339096A (en) |
BR (1) | BR9600353A (en) |
CA (1) | CA2168822A1 (en) |
DE (1) | DE69637081T2 (en) |
ZA (1) | ZA96936B (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0837084A2 (en) * | 1996-10-17 | 1998-04-22 | United States Surgical Corporation | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
WO2000015270A1 (en) * | 1998-09-10 | 2000-03-23 | Schering Aktiengesellschaft | Coated medical devices and implants |
US6207767B1 (en) | 1994-07-22 | 2001-03-27 | United States Surgical Corporation | Bioabsorbable branched polymer containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
FR2812551A1 (en) * | 2000-08-07 | 2002-02-08 | Virsol | PHARMACEUTICAL FORM COMPRISING A METHYLIDENE MALONATE-BASED SUPPORT MATERIAL AND A CELLULAR REGULATION FACTOR |
EP1169979A3 (en) * | 2000-06-28 | 2003-08-06 | Ethicon, Inc. | Method for fixing a graft in a bone tunnel |
DE10212348A1 (en) * | 2002-03-14 | 2003-09-25 | Aesculap Ag & Co Kg | Curable composition based on a component curable at body temperature and a reabsorbed component obtained by catalytic polymerization useful for bone cementation |
EP1401977A1 (en) * | 2001-06-29 | 2004-03-31 | Chemence, Inc. | Solid dyanoacrylate adhesive composition and method for its use |
US7097907B2 (en) | 1994-07-22 | 2006-08-29 | United States Surgical Corporation | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
EP1642601A3 (en) * | 2004-09-27 | 2007-12-05 | Ethicon, Inc. | Suture anchor and void filler combination |
EP2462961A3 (en) * | 2010-12-08 | 2014-08-27 | Biotronik AG | Implant made of biocorrodible material and with a coating containing a tissue adhesive |
Families Citing this family (123)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5468253A (en) * | 1993-01-21 | 1995-11-21 | Ethicon, Inc. | Elastomeric medical device |
ATE330644T1 (en) | 1995-12-18 | 2006-07-15 | Angiotech Biomaterials Corp | CROSS-LINKED POLYMER MATERIALS AND METHODS FOR USE THEREOF |
US6833408B2 (en) | 1995-12-18 | 2004-12-21 | Cohesion Technologies, Inc. | Methods for tissue repair using adhesive materials |
US7883693B2 (en) | 1995-12-18 | 2011-02-08 | Angiodevice International Gmbh | Compositions and systems for forming crosslinked biomaterials and methods of preparation of use |
DE19641335A1 (en) * | 1996-10-08 | 1998-04-09 | Inst Textil & Faserforschung | Triblock terpolymer, its use in surgical sutures and manufacturing methods |
US5718717A (en) | 1996-08-19 | 1998-02-17 | Bonutti; Peter M. | Suture anchor |
DE19641334A1 (en) * | 1996-10-08 | 1998-04-09 | Inst Textil & Faserforschung | Triblock terpolymer, its use in medical products and manufacturing processes |
US5906617A (en) * | 1997-08-15 | 1999-05-25 | Meislin; Robert J. | Surgical repair with hook-and-loop fastener |
US20050245966A1 (en) * | 1997-12-17 | 2005-11-03 | Hammerslag Julius G | Controlled viscosity tissue adhesive |
WO1999030629A1 (en) | 1997-12-17 | 1999-06-24 | Hemodynamics, Inc. | Sealing media for surgery and wound closure |
US6045551A (en) | 1998-02-06 | 2000-04-04 | Bonutti; Peter M. | Bone suture |
JP3412039B2 (en) * | 1998-02-12 | 2003-06-03 | 株式会社ビーエムジー | Surgical adhesive composition |
US6086593A (en) | 1998-06-30 | 2000-07-11 | Bonutti; Peter M. | Method and apparatus for use in operating on a bone |
US6099531A (en) * | 1998-08-20 | 2000-08-08 | Bonutti; Peter M. | Changing relationship between bones |
FR2789314B1 (en) * | 1999-02-09 | 2001-04-27 | Virsol | WOUND SUTURE MATERIAL BASED ON METHYLIDENE MALONATE |
WO2000072761A1 (en) * | 1999-05-29 | 2000-12-07 | Tyco Health Care Group, Lp | Bioabsorbable blends and surgical articles therefrom |
AU2007221760B2 (en) * | 1999-05-29 | 2010-07-29 | Covidien Lp | Bioabsorbable blends and surgical articles therefrom |
US6840995B2 (en) * | 1999-07-14 | 2005-01-11 | Calcitec, Inc. | Process for producing fast-setting, bioresorbable calcium phosphate cements |
US7094282B2 (en) * | 2000-07-13 | 2006-08-22 | Calcitec, Inc. | Calcium phosphate cement, use and preparation thereof |
US7169373B2 (en) * | 1999-07-14 | 2007-01-30 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface and process for preparing the same |
US7270705B2 (en) | 1999-07-14 | 2007-09-18 | Jiin-Huey Chern Lin | Method of increasing working time of tetracalcium phosphate cement paste |
US6960249B2 (en) * | 1999-07-14 | 2005-11-01 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface |
US6368343B1 (en) | 2000-03-13 | 2002-04-09 | Peter M. Bonutti | Method of using ultrasonic vibration to secure body tissue |
US6447516B1 (en) | 1999-08-09 | 2002-09-10 | Peter M. Bonutti | Method of securing tissue |
US6635073B2 (en) | 2000-05-03 | 2003-10-21 | Peter M. Bonutti | Method of securing body tissue |
US7156915B2 (en) * | 2000-07-13 | 2007-01-02 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) with surface whiskers and method of making same |
US7160382B2 (en) * | 2000-07-13 | 2007-01-09 | Calcitec, Inc. | Calcium phosphate cements made from (TTCP) with surface whiskers and process for preparing same |
US6605090B1 (en) * | 2000-10-25 | 2003-08-12 | Sdgi Holdings, Inc. | Non-metallic implant devices and intra-operative methods for assembly and fixation |
US6666870B2 (en) | 2001-01-05 | 2003-12-23 | Robert A Dixon | Method utilizing chemical bonding to improve the bone screw fixation interface |
US6632235B2 (en) | 2001-04-19 | 2003-10-14 | Synthes (U.S.A.) | Inflatable device and method for reducing fractures in bone and in treating the spine |
US7303817B2 (en) | 2001-10-24 | 2007-12-04 | Weitao Jia | Dental filling material |
US7750063B2 (en) | 2001-10-24 | 2010-07-06 | Pentron Clinical Technologies, Llc | Dental filling material |
US7204874B2 (en) | 2001-10-24 | 2007-04-17 | Pentron Clinical Technologies, Llc | Root canal filling material |
US6719765B2 (en) | 2001-12-03 | 2004-04-13 | Bonutti 2003 Trust-A | Magnetic suturing system and method |
US7255874B1 (en) | 2001-12-21 | 2007-08-14 | Closure Medical Corporation | Biocompatible polymers and adhesives: compositions, methods of making and uses related thereto |
AR038680A1 (en) | 2002-02-19 | 2005-01-26 | Synthes Ag | INTERVERTEBRAL IMPLANT |
CA2477220C (en) | 2002-03-14 | 2007-11-06 | Jeffrey E. Yeung | Suture anchor and approximating device |
US20030216777A1 (en) * | 2002-05-16 | 2003-11-20 | Yin-Chun Tien | Method of enhancing healing of interfacial gap between bone and tendon or ligament |
EP2457541A1 (en) | 2003-02-06 | 2012-05-30 | Synthes GmbH | Implant between vertebrae |
US6994726B2 (en) * | 2004-05-25 | 2006-02-07 | Calcitec, Inc. | Dual function prosthetic bone implant and method for preparing the same |
US7118705B2 (en) | 2003-08-05 | 2006-10-10 | Calcitec, Inc. | Method for making a molded calcium phosphate article |
US7163651B2 (en) * | 2004-02-19 | 2007-01-16 | Calcitec, Inc. | Method for making a porous calcium phosphate article |
CA2545185A1 (en) * | 2003-11-07 | 2005-05-26 | Calcitec, Inc. | Spinal fusion procedure using an injectable bone substitute |
CN104174071A (en) * | 2004-04-28 | 2014-12-03 | 安希奥设备国际有限责任公司 | Compositions and systems for forming crosslinked biomaterials and associated methods of preparation and use |
US7776041B1 (en) | 2004-07-12 | 2010-08-17 | Biomet Sports Medicine, Llc | Method and apparatus for implanting a suture anchor |
WO2006034128A2 (en) | 2004-09-17 | 2006-03-30 | Angiotech Biomaterials Corporation | Multifunctional compounds for forming crosslinked biomaterials and methods of preparation and use |
CA2584022C (en) * | 2004-10-18 | 2013-12-10 | Tyco Healthcare Group Lp | Surgical fasteners coated with wound treatment materials |
US7455682B2 (en) * | 2004-10-18 | 2008-11-25 | Tyco Healthcare Group Lp | Structure containing wound treatment material |
US7758594B2 (en) | 2005-05-20 | 2010-07-20 | Neotract, Inc. | Devices, systems and methods for treating benign prostatic hyperplasia and other conditions |
US8425535B2 (en) | 2005-05-20 | 2013-04-23 | Neotract, Inc. | Multi-actuating trigger anchor delivery system |
US9149266B2 (en) | 2005-05-20 | 2015-10-06 | Neotract, Inc. | Deforming anchor device |
US8529584B2 (en) * | 2005-05-20 | 2013-09-10 | Neotract, Inc. | Median lobe band implant apparatus and method |
US8668705B2 (en) | 2005-05-20 | 2014-03-11 | Neotract, Inc. | Latching anchor device |
US8157815B2 (en) | 2005-05-20 | 2012-04-17 | Neotract, Inc. | Integrated handle assembly for anchor delivery system |
US9364212B2 (en) | 2005-05-20 | 2016-06-14 | Neotract, Inc. | Suture anchoring devices and methods for use |
US8394113B2 (en) | 2005-05-20 | 2013-03-12 | Neotract, Inc. | Coiled anchor device |
US7896891B2 (en) | 2005-05-20 | 2011-03-01 | Neotract, Inc. | Apparatus and method for manipulating or retracting tissue and anatomical structure |
US8834492B2 (en) * | 2005-05-20 | 2014-09-16 | Neotract, Inc. | Continuous indentation lateral lobe apparatus and method |
US8945152B2 (en) | 2005-05-20 | 2015-02-03 | Neotract, Inc. | Multi-actuating trigger anchor delivery system |
US8603106B2 (en) | 2005-05-20 | 2013-12-10 | Neotract, Inc. | Integrated handle assembly for anchor delivery system |
US9549739B2 (en) | 2005-05-20 | 2017-01-24 | Neotract, Inc. | Devices, systems and methods for treating benign prostatic hyperplasia and other conditions |
US9504461B2 (en) | 2005-05-20 | 2016-11-29 | Neotract, Inc. | Anchor delivery system |
US10925587B2 (en) | 2005-05-20 | 2021-02-23 | Neotract, Inc. | Anchor delivery system |
US10195014B2 (en) | 2005-05-20 | 2019-02-05 | Neotract, Inc. | Devices, systems and methods for treating benign prostatic hyperplasia and other conditions |
US7645286B2 (en) * | 2005-05-20 | 2010-01-12 | Neotract, Inc. | Devices, systems and methods for retracting, lifting, compressing, supporting or repositioning tissues or anatomical structures |
US8491606B2 (en) * | 2005-05-20 | 2013-07-23 | Neotract, Inc. | Median lobe retraction apparatus and method |
US8333776B2 (en) | 2005-05-20 | 2012-12-18 | Neotract, Inc. | Anchor delivery system |
US8628542B2 (en) | 2005-05-20 | 2014-01-14 | Neotract, Inc. | Median lobe destruction apparatus and method |
WO2007098288A2 (en) | 2006-02-27 | 2007-08-30 | Synthes (U.S.A.) | Intervertebral implant with fixation geometry |
US7988711B2 (en) | 2006-09-21 | 2011-08-02 | Warsaw Orthopedic, Inc. | Low profile vertebral stabilization systems and methods |
US20080110961A1 (en) * | 2006-11-10 | 2008-05-15 | Ethicon Endo-Surgery, Inc. | Initiator Coating of Staples |
US8485411B2 (en) | 2007-05-16 | 2013-07-16 | The Invention Science Fund I, Llc | Gentle touch surgical stapler |
US7823761B2 (en) | 2007-05-16 | 2010-11-02 | The Invention Science Fund I, Llc | Maneuverable surgical stapler |
US7832611B2 (en) * | 2007-05-16 | 2010-11-16 | The Invention Science Fund I, Llc | Steerable surgical stapler |
US7798385B2 (en) * | 2007-05-16 | 2010-09-21 | The Invention Science Fund I, Llc | Surgical stapling instrument with chemical sealant |
US7922064B2 (en) * | 2007-05-16 | 2011-04-12 | The Invention Science Fund, I, LLC | Surgical fastening device with cutter |
US7810691B2 (en) | 2007-05-16 | 2010-10-12 | The Invention Science Fund I, Llc | Gentle touch surgical stapler |
US8758366B2 (en) | 2007-07-09 | 2014-06-24 | Neotract, Inc. | Multi-actuating trigger anchor delivery system |
US8500947B2 (en) | 2007-11-15 | 2013-08-06 | Covidien Lp | Speeding cure rate of bioadhesives |
KR20100105580A (en) | 2007-11-16 | 2010-09-29 | 신세스 게엠바하 | Low profile intervertebral implant |
WO2010014825A1 (en) * | 2008-07-30 | 2010-02-04 | Neotract, Inc. | Slotted anchor device |
CN102112064B (en) * | 2008-07-30 | 2014-06-18 | 新域公司 | Anchor delivery system with replaceable cartridge |
WO2010054208A1 (en) | 2008-11-07 | 2010-05-14 | Synthes Usa, Llc | Vertebral interbody spacer and coupled plate assembly |
BRPI1008924A2 (en) | 2009-03-16 | 2017-06-06 | Synthes Gmbh | System and method for stabilizing vertebra in spine surgery through a lateral access channel |
US8106234B2 (en) * | 2009-05-07 | 2012-01-31 | OptMed, Inc | Methylidene malonate process |
US8975435B2 (en) * | 2009-05-07 | 2015-03-10 | Optmed, Inc. | Methylidene malonate process |
US9028553B2 (en) | 2009-11-05 | 2015-05-12 | DePuy Synthes Products, Inc. | Self-pivoting spinal implant and associated instrumentation |
US10414839B2 (en) | 2010-10-20 | 2019-09-17 | Sirrus, Inc. | Polymers including a methylene beta-ketoester and products formed therefrom |
US9828324B2 (en) | 2010-10-20 | 2017-11-28 | Sirrus, Inc. | Methylene beta-diketone monomers, methods for making methylene beta-diketone monomers, polymerizable compositions and products formed therefrom |
US9279022B1 (en) | 2014-09-08 | 2016-03-08 | Sirrus, Inc. | Solution polymers including one or more 1,1-disubstituted alkene compounds, solution polymerization methods, and polymer compositions |
US9249265B1 (en) | 2014-09-08 | 2016-02-02 | Sirrus, Inc. | Emulsion polymers including one or more 1,1-disubstituted alkene compounds, emulsion methods, and polymer compositions |
KR20140092225A (en) | 2010-10-20 | 2014-07-23 | 바이오포믹스, 인크. | Synthesis of methylene malonates substantially free of impurities |
US9549760B2 (en) * | 2010-10-29 | 2017-01-24 | Kyphon Sarl | Reduced extravasation of bone cement |
WO2012088238A2 (en) | 2010-12-21 | 2012-06-28 | Synthes Usa, Llc | Intervertebral implants, systems, and methods of use |
US9161749B2 (en) | 2011-04-14 | 2015-10-20 | Neotract, Inc. | Method and apparatus for treating sexual dysfunction |
CA2853073A1 (en) | 2011-10-19 | 2013-04-25 | Bioformix Inc. | Methylene beta-diketone monomers, methods for making methylene beta-diketone monomers, polymerizable compositions and products formed therefrom |
US10292801B2 (en) | 2012-03-29 | 2019-05-21 | Neotract, Inc. | System for delivering anchors for treating incontinence |
CA2869108A1 (en) | 2012-03-30 | 2013-10-03 | Bioformix Inc. | Methods for activating polymerizable compositions, polymerizable systems, and products formed thereby |
CA2869115A1 (en) | 2012-03-30 | 2013-10-03 | Bioformix Inc. | Ink and coating formulations and polymerizable systems for producing the same |
EP3153530B1 (en) | 2012-03-30 | 2021-02-24 | Sirrus, Inc. | Composite and laminate articles and polymerizable systems for producing the same |
WO2013181600A2 (en) | 2012-06-01 | 2013-12-05 | Bioformix Inc. | Optical material and articles formed therefrom |
US10130353B2 (en) | 2012-06-29 | 2018-11-20 | Neotract, Inc. | Flexible system for delivering an anchor |
CN105008438B (en) | 2012-11-16 | 2019-10-22 | 拜奥福米克斯公司 | Plastics bonding system and method |
EP2926368B1 (en) | 2012-11-30 | 2020-04-08 | Sirrus, Inc. | Electronic assembly |
US10022245B2 (en) | 2012-12-17 | 2018-07-17 | DePuy Synthes Products, Inc. | Polyaxial articulating instrument |
CN110204441A (en) | 2013-01-11 | 2019-09-06 | 瑟拉斯公司 | The method for obtaining methylene malonate by the approach of bis- (methylol) malonates |
US9315597B2 (en) | 2014-09-08 | 2016-04-19 | Sirrus, Inc. | Compositions containing 1,1-disubstituted alkene compounds for preparing polymers having enhanced glass transition temperatures |
US9416091B1 (en) | 2015-02-04 | 2016-08-16 | Sirrus, Inc. | Catalytic transesterification of ester compounds with groups reactive under transesterification conditions |
US9867718B2 (en) | 2014-10-22 | 2018-01-16 | DePuy Synthes Products, Inc. | Intervertebral implants, systems, and methods of use |
US10501400B2 (en) | 2015-02-04 | 2019-12-10 | Sirrus, Inc. | Heterogeneous catalytic transesterification of ester compounds with groups reactive under transesterification conditions |
US9334430B1 (en) | 2015-05-29 | 2016-05-10 | Sirrus, Inc. | Encapsulated polymerization initiators, polymerization systems and methods using the same |
US9217098B1 (en) | 2015-06-01 | 2015-12-22 | Sirrus, Inc. | Electroinitiated polymerization of compositions having a 1,1-disubstituted alkene compound |
US9518001B1 (en) | 2016-05-13 | 2016-12-13 | Sirrus, Inc. | High purity 1,1-dicarbonyl substituted-1-alkenes and methods for their preparation |
US10428177B2 (en) | 2016-06-03 | 2019-10-01 | Sirrus, Inc. | Water absorbing or water soluble polymers, intermediate compounds, and methods thereof |
US9617377B1 (en) | 2016-06-03 | 2017-04-11 | Sirrus, Inc. | Polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
US10196481B2 (en) | 2016-06-03 | 2019-02-05 | Sirrus, Inc. | Polymer and other compounds functionalized with terminal 1,1-disubstituted alkene monomer(s) and methods thereof |
US9567475B1 (en) | 2016-06-03 | 2017-02-14 | Sirrus, Inc. | Coatings containing polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
KR102571880B1 (en) | 2017-06-02 | 2023-08-28 | 아르끄마 프랑스 | Curable Compositions and Uses Thereof |
US10966843B2 (en) | 2017-07-18 | 2021-04-06 | DePuy Synthes Products, Inc. | Implant inserters and related methods |
US11045331B2 (en) | 2017-08-14 | 2021-06-29 | DePuy Synthes Products, Inc. | Intervertebral implant inserters and related methods |
JP7150871B2 (en) | 2017-12-23 | 2022-10-11 | テレフレックス ライフ サイエンシズ リミテッド | Expandable tissue engagement device and method |
EP3999607A2 (en) | 2019-07-19 | 2022-05-25 | Arkema France | Curable compositions useful for obtaining non-sensitizing cured products |
JP7296522B2 (en) | 2020-08-03 | 2023-06-22 | テレフレックス ライフ サイエンシズ リミテッド | Handle cartridge system for medical intervention |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2308360A1 (en) * | 1975-04-23 | 1976-11-19 | Ethicon Inc | ADHESIVE APPLICABLE IN SURGERY |
US4186190A (en) * | 1978-11-13 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Navy | Method of treating burns using a poly-ε-caprolactone |
US4440789A (en) * | 1982-11-16 | 1984-04-03 | Ethicon, Inc. | Synthetic absorbable hemostatic composition |
EP0290983A2 (en) * | 1987-05-15 | 1988-11-17 | Henkel Kommanditgesellschaft auf Aktien | Resorbable bone wax |
WO1990003768A1 (en) * | 1988-10-03 | 1990-04-19 | Southern Research Institute | Biodegradable in-situ forming implants |
EP0425200A1 (en) * | 1989-10-19 | 1991-05-02 | Nobuo Nakabayashi | Bone cement composition, cured product thereof, implant material and process for the preparation of the same |
EP0543765A1 (en) * | 1991-11-22 | 1993-05-26 | Maria Gertruda Boltong | Process for the preparation of calcium phosphate cements and their application as bio-materials |
WO1993020859A1 (en) * | 1992-04-20 | 1993-10-28 | Board Of Regents Of The University Of Washington | Sustained release compositions for delivery of growth factors |
US5328687A (en) * | 1993-03-31 | 1994-07-12 | Tri-Point Medical L.P. | Biocompatible monomer and polymer compositions |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE33161E (en) * | 1982-04-29 | 1990-02-06 | American Dental Association Health Foundation | Combinations of sparingly soluble calcium phosphates in slurries and pastes as mineralizers and cements |
USRE33221E (en) * | 1982-04-29 | 1990-05-22 | American Dental Association Health Foundation | Dental restorative cement pastes |
US4612053A (en) * | 1983-10-06 | 1986-09-16 | American Dental Association Health Foundation | Combinations of sparingly soluble calcium phosphates in slurries and pastes as mineralizers and cements |
US4668295A (en) * | 1985-04-25 | 1987-05-26 | University Of Dayton | Surgical cements |
GB2197329B (en) * | 1986-09-10 | 1990-01-10 | Showa Denko Kk | Hard tissue substitute composition |
JP2558262B2 (en) * | 1986-11-04 | 1996-11-27 | 住友大阪セメント 株式会社 | Artificial joint fixation material |
DE3869850D1 (en) * | 1987-07-10 | 1992-05-14 | Asahi Optical Co Ltd | COMPOSITION FOR PRODUCING A HARDENABLE CALCIUM PHOSPHATE-LIKE MATERIAL AND METHOD FOR PRODUCING SUCH A MATERIAL. |
JP2548745B2 (en) * | 1987-10-15 | 1996-10-30 | 住友大阪セメント株式会社 | Bone cement composition |
US5178845A (en) * | 1988-04-20 | 1993-01-12 | Norian Corporation | Intimate mixture of calcium and phosphate sources as precursor to hydroxyapatite |
US5053212A (en) * | 1988-04-20 | 1991-10-01 | Norian Corporation | Intimate mixture of calcium and phosphate sources as precursor to hydroxyapatite |
US4880610A (en) * | 1988-04-20 | 1989-11-14 | Norian Corporation | In situ calcium phosphate minerals--method and composition |
JPH0773602B2 (en) * | 1988-07-23 | 1995-08-09 | 新田ゼラチン株式会社 | Medical and dental curable materials |
JPH0241171A (en) * | 1988-07-28 | 1990-02-09 | Mamoru Nagase | Artificial bone cured and formed by mixing tricalcium phosphate, acid, protein, water and hydroxyapatite |
US5223029A (en) * | 1988-08-10 | 1993-06-29 | Nitta Gelatin Inc. | Hardening material for medical and dental use |
US5296026A (en) * | 1988-12-02 | 1994-03-22 | Monroe Eugene A | Phosphate glass cement |
DE69012260T2 (en) * | 1989-08-29 | 1995-01-12 | Univ Kyoto | Bioactive cement. |
JPH03128063A (en) * | 1989-10-16 | 1991-05-31 | Natl Inst For Res In Inorg Mater | Water-curable type calcium phosphate cement composition |
JP2780120B2 (en) * | 1989-11-08 | 1998-07-30 | 三金工業株式会社 | Hardening calcium phosphate dental composition |
JPH03273679A (en) * | 1990-03-23 | 1991-12-04 | Matsushita Electron Corp | Solid-state image sensing device |
EP0520690B1 (en) * | 1991-06-26 | 1995-11-02 | Nitta Gelatin Inc. | Calcium phosphate type hardening material for repairing living hard tissue |
JPH0564658A (en) * | 1991-09-09 | 1993-03-19 | Nippon Electric Glass Co Ltd | Bioactive cement and manufacture thereof |
JPH0564659A (en) * | 1991-09-09 | 1993-03-19 | Nippon Electric Glass Co Ltd | Bioactive cement and manufacture thereof |
US5281265A (en) * | 1992-02-03 | 1994-01-25 | Liu Sung Tsuen | Resorbable surgical cements |
US5218035A (en) * | 1992-02-03 | 1993-06-08 | Liu Sung Tsuen | Phosphate-containing surgical cements |
-
1995
- 1995-02-07 US US08/385,015 patent/US5550172A/en not_active Expired - Lifetime
-
1996
- 1996-02-05 CA CA002168822A patent/CA2168822A1/en not_active Abandoned
- 1996-02-06 DE DE69637081T patent/DE69637081T2/en not_active Expired - Fee Related
- 1996-02-06 EP EP96300790A patent/EP0727230B1/en not_active Expired - Lifetime
- 1996-02-06 ZA ZA9600936A patent/ZA96936B/en unknown
- 1996-02-06 AU AU43390/96A patent/AU4339096A/en not_active Abandoned
- 1996-02-07 BR BR9600353A patent/BR9600353A/en not_active Application Discontinuation
- 1996-02-07 JP JP8044075A patent/JPH08252306A/en active Pending
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2308360A1 (en) * | 1975-04-23 | 1976-11-19 | Ethicon Inc | ADHESIVE APPLICABLE IN SURGERY |
US4186190A (en) * | 1978-11-13 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Navy | Method of treating burns using a poly-ε-caprolactone |
US4440789A (en) * | 1982-11-16 | 1984-04-03 | Ethicon, Inc. | Synthetic absorbable hemostatic composition |
EP0290983A2 (en) * | 1987-05-15 | 1988-11-17 | Henkel Kommanditgesellschaft auf Aktien | Resorbable bone wax |
WO1990003768A1 (en) * | 1988-10-03 | 1990-04-19 | Southern Research Institute | Biodegradable in-situ forming implants |
EP0425200A1 (en) * | 1989-10-19 | 1991-05-02 | Nobuo Nakabayashi | Bone cement composition, cured product thereof, implant material and process for the preparation of the same |
EP0543765A1 (en) * | 1991-11-22 | 1993-05-26 | Maria Gertruda Boltong | Process for the preparation of calcium phosphate cements and their application as bio-materials |
WO1993020859A1 (en) * | 1992-04-20 | 1993-10-28 | Board Of Regents Of The University Of Washington | Sustained release compositions for delivery of growth factors |
US5328687A (en) * | 1993-03-31 | 1994-07-12 | Tri-Point Medical L.P. | Biocompatible monomer and polymer compositions |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6207767B1 (en) | 1994-07-22 | 2001-03-27 | United States Surgical Corporation | Bioabsorbable branched polymer containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
US7097907B2 (en) | 1994-07-22 | 2006-08-29 | United States Surgical Corporation | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
EP0837084A2 (en) * | 1996-10-17 | 1998-04-22 | United States Surgical Corporation | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
EP0837084A3 (en) * | 1996-10-17 | 1998-12-09 | United States Surgical Corporation | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
WO2000015270A1 (en) * | 1998-09-10 | 2000-03-23 | Schering Aktiengesellschaft | Coated medical devices and implants |
EP1169979A3 (en) * | 2000-06-28 | 2003-08-06 | Ethicon, Inc. | Method for fixing a graft in a bone tunnel |
WO2002011779A1 (en) * | 2000-08-07 | 2002-02-14 | Virsol | Pharmaceutical form comprising a cell regulating factor and/or a cell proliferation promoter |
FR2812551A1 (en) * | 2000-08-07 | 2002-02-08 | Virsol | PHARMACEUTICAL FORM COMPRISING A METHYLIDENE MALONATE-BASED SUPPORT MATERIAL AND A CELLULAR REGULATION FACTOR |
EP1401977A1 (en) * | 2001-06-29 | 2004-03-31 | Chemence, Inc. | Solid dyanoacrylate adhesive composition and method for its use |
EP1401977A4 (en) * | 2001-06-29 | 2005-07-27 | Chemence Inc | Solid dyanoacrylate adhesive composition and method for its use |
DE10212348A1 (en) * | 2002-03-14 | 2003-09-25 | Aesculap Ag & Co Kg | Curable composition based on a component curable at body temperature and a reabsorbed component obtained by catalytic polymerization useful for bone cementation |
EP1642601A3 (en) * | 2004-09-27 | 2007-12-05 | Ethicon, Inc. | Suture anchor and void filler combination |
EP2462961A3 (en) * | 2010-12-08 | 2014-08-27 | Biotronik AG | Implant made of biocorrodible material and with a coating containing a tissue adhesive |
Also Published As
Publication number | Publication date |
---|---|
DE69637081T2 (en) | 2008-01-17 |
EP0727230B1 (en) | 2007-05-16 |
JPH08252306A (en) | 1996-10-01 |
ZA96936B (en) | 1997-08-06 |
AU4339096A (en) | 1996-08-15 |
US5550172A (en) | 1996-08-27 |
BR9600353A (en) | 1998-01-27 |
DE69637081D1 (en) | 2007-06-28 |
EP0727230A3 (en) | 1999-02-03 |
CA2168822A1 (en) | 1996-08-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5550172A (en) | Utilization of biocompatible adhesive/sealant materials for securing surgical devices | |
US5668288A (en) | Polyester ionomers for implant fabrication | |
CA2299935C (en) | Bioabsorbable materials and medical devices made therefrom | |
JP3556773B2 (en) | High-glycolide-containing poly (glycolide-co-p-dioxanone) copolymer with high strength, rapid absorbability and melt processability | |
EP0107591B2 (en) | Absorbable surgical devices | |
US5747390A (en) | Hard tissue bone cements and substitutes | |
JP3161729B2 (en) | Method for producing medically applicable article from copolymer of lactide and ε-caprolactone | |
US5703200A (en) | Absorbable copolymers and blends of 6,6-dialkyl-1,4-dioxepan-2-one and its cyclic dimer | |
JP3218148B2 (en) | Copolymer of aromatic anhydride and aliphatic ester | |
US5082925A (en) | Homopolymers and copolymers of salicylate lactones | |
US20030120029A1 (en) | Amorphous polymeric polyaxial initiators and compliant crystalline copolymers therefrom | |
US5442032A (en) | Copolymers of 1,4-dioxepan-2-one and 1,5,8,12-tetraoxacyclotetradecane-7-14-dione | |
JPH09132639A (en) | Absorbable, biocompatible segment copolymer and its production | |
JPH08333443A (en) | Absorbent polyoxa ester | |
JPH0363974B2 (en) | ||
EP0210226A4 (en) | Medical putty for tissue augmentation. | |
CA2218447C (en) | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom | |
Feng et al. | Synthesis and Characterization of New Block Copolymers with Poly (ethylene oxide) and Poly [3 (S)‐sec‐butylmorpholine‐2, 5‐dione] Sequences | |
JP2992694B2 (en) | Hydroxycarboxylic acid copolymer | |
US6297350B1 (en) | Process for the preparation of copolyesters | |
Super et al. | Incorporation of salicylates into poly (L-lactide) | |
JPH06508388A (en) | Copolymers based on cyclic esters and their use as surgical implants | |
US5236702A (en) | Composition and method for blood coagulation on hard body tissues | |
Shalaby | Absorbable Polymers with Engineered Biomedical Properties | |
MXPA97001991A (en) | Copolymer and absorbable mixes of 6,6-dialquil-1,4-dioxepan-2-ona and its dimero cicl |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): DE FR GB IT |
|
PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
AK | Designated contracting states |
Kind code of ref document: A3 Designated state(s): DE FR GB IT |
|
17P | Request for examination filed |
Effective date: 19990712 |
|
17Q | First examination report despatched |
Effective date: 20010523 |
|
RIC1 | Information provided on ipc code assigned before grant |
Ipc: A61L 24/02 20060101AFI20061004BHEP |
|
GRAC | Information related to communication of intention to grant a patent modified |
Free format text: ORIGINAL CODE: EPIDOSCIGR1 |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
GRAS | Grant fee paid |
Free format text: ORIGINAL CODE: EPIDOSNIGR3 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): DE FR GB IT |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D |
|
REF | Corresponds to: |
Ref document number: 69637081 Country of ref document: DE Date of ref document: 20070628 Kind code of ref document: P |
|
ET | Fr: translation filed | ||
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
26N | No opposition filed |
Effective date: 20080219 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT Effective date: 20070516 |
|
PGRI | Patent reinstated in contracting state [announced from national office to epo] |
Ref country code: IT Effective date: 20080801 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 20090129 Year of fee payment: 14 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20090204 Year of fee payment: 14 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20090214 Year of fee payment: 14 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20090213 Year of fee payment: 14 |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20100206 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST Effective date: 20101029 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100301 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100901 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100206 Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20100206 |